Dr. Ramy Aziz spent four months annotating a small portion of a single Streptococcus genome when he was working toward his Ph.D. in microbiology and immunology in 2004. By 2010, he could analyze a few Streptococcus genomes in under two days using RAST (Rapid Annotation using Subsystem Technology), a server that provides a fully automated annotation service for bacterial genomes. Dr. Aziz, now professor and chair of the Department of Microbiology and Immunology, Faculty of Pharmacy at Cairo University in Egypt, fully annotated another Streptococcus genome sequence in 2018 in only 6 minutes using the Pathosystems Resource Integration Center (PATRIC).
PATRIC is one of six NIAID-funded Bioinformatics Resource Centers (BRCs) for Infectious Diseases. NIAID initiated the BRCs in 2004 to collect, archive, update and integrate a variety of research data and make it freely-available to the scientific community through resource-friendly interfaces with computational analysis tools.
Each BRC specializes in a different group of pathogens: PATRIC focuses on bacterial species, while the other BRCs specialize in viral families (including influenza), eukaryotic pathogens (such as fungi) and invertebrate carriers of infectious diseases (such as mosquitoes and ticks). The BRCs compile large datasets in a standardized way, allowing scientists to perform analyses more efficiently.
“All scientists do not necessarily have the resources to set up the infrastructure to analyze large datasets,” said Ishwar Chandramouliswaran, program officer in the Office of Genomics and Advanced Technologies in NIAID’s Division of Microbiology and Infectious Diseases. He notes that rather than spending days using specialized equipment and tools to set up an analysis, scientists can visit the PATRIC website and click from a list of services. The resource center offers genome assembly, annotation and analysis, as well as RNA sequencing, and interactive phylogenetic trees (showing the evolutionary relationships among organisms), among other services.
Scientists also can upload their own data to a private workspace and compare it against public data collections. Currently, PATRIC has about 30,000 registered users and contains diverse data of approximately 150,000 genomes and associated information.
“Each year, we’re expanding the number of services and tools available to the scientific community, and our impact is growing,” said Rick Stevens, principal investigator of PATRIC, and professor of Computer Science at the University of Chicago. “Researchers can now do analyses that would have been too costly or time-consuming just a few years ago.”
PATRIC offers various tools for comparative analyses, including a protein family sorter and heatmap that provide a broad view of the distribution of protein families across a set of genomes. The resource center collects data from public repositories like GenBank and ensures genomic features are consistently annotated using the RAST system.
“This enables an ‘apples to apples’ comparative analysis across all genomes,” said Jim Davis, a computational biologist part of the PATRIC team at the University of Chicago. NIAID supports PATRIC through a contract awarded to the University of Chicago.
These large-scale genomic and other analyses can help scientists assess the function of specific genes, identify markers for diagnosing a particular bacterial infection, detect a microbe’s virulence factors (molecules that enable a pathogen to infect a host), or discover new bacterial resistance mechanisms.
“Our team of annotators has been integrating data from the literature and public resources to build one of the most accurate and consistent environments for annotating proteins involved in antimicrobial resistance,” said Davis. “We also have been collecting data where researchers have performed laboratory antimicrobial susceptibility tests and sequenced the genomes corresponding to these isolates,” he added.
Dr. Aziz said that PATRIC offers valuable tools for researchers like him who are interested in finding alternative treatments for infectious diseases, including bacteriophage (phage) therapy. Phage therapy uses viruses that only affect bacteria to reduce or eliminate those bacteria in humans. Dr. Aziz uses PATRIC as a teaching resource and has a student team using the platform to improve phage analysis tools. Another student group, called “The AMR Hunters,” is using PATRIC to annotate all known antimicrobial resistance genes and their variants.
“I am amazed that we now have the tools to use genome sequencing and fast annotation to understand the causative agents of disease, which allows us already to save lives, and I hope these tools will be soon generalized in hospitals around the world,” said Dr. Aziz.